Phenotypic expansion of the interstitial 16p13.3 duplication: a case report and review of the literature

Abstract

Genotype-phenotype analysis of at least 25 individuals with interstitial 16p13.3 duplications defines a recognizable syndrome associated with duplication of a critical Rubinstein-Taybi region encompassing only the CREBBP gene. Nevertheless, variable or incompletely penetrant phenotype has been reported previously. We here report a case of a 5-year old boy with a recognizable phenotype of this syndrome, including intellectual disability, mild arthrogryposis, small and proximally implanted thumbs and characteristic facial features. In addition, growth delay, microcephaly and distinguishable structural brain MRI abnormalities were observed. A de novo 1.5 Mb interstitial duplication of 16p13.3 was detected by SNP-array and fluorescence in situ hybridization (FISH). Short tandem repeat polymorphism (STRP) analysis with marker D16S475 indicated that the duplication was formed before maternal meiosis II. Our findings highlight the variable clinical features and further expand the phenotypic spectrum correlated with this lately proposed syndrome.

Keywords: ASD; BAC; CNV; CREBBP; DD; DQ; F; FISH; Growth delay; ID; IUGR; Intellectual disability; Interstitial 16p13.3 duplications; M; MRI; SD; SNP; SNP array; STRP; atrial septal defect; bacterial artificial chromosome; copy number variation; cyclic AMP response element binding protein; dUTP; deoxyuridine triphosphate; development quotient; developmental delay; female; fluorescence in situ hybridization; intellectual disability; intrauterine growth retardation; magnetic resonance imaging; male; short tandem repeat polymorphism; single nucleotide polymorphism; standard deviation.